VEGF gene transfer to prevent coronary artery restenosis

本研究旨在研究血管内皮生长因子-1(VEGFA)基因编码165个氨基酸的裸露DNA作为PTCA辅助的动脉基因转移。该提案有以下三个具体目标。具体目的#1：确定在冠状动脉狭窄或闭塞的患者(PTCA)经皮冠状动脉腔内成形术(PTCA)后转导phVEGF165以加速再内皮化(RET)的安全性。特定目的#2：获得关于转导phVEGF165预防冠状动脉再狭窄的生物活性的初步数据。具体目标#3：确定pVEGF165冠状动脉基因转移对冠状动脉病变进展的影响，涉及冠状动脉病变部位而不是PTCA靶点。在基因转移后，将在这项研究中登记的患者中进行各种评估。将进行一系列临床检查--包括标准病史和身体检查--以及标准实验室测试，以证明phVEGF165冠状动脉基因转移的安全性。将通过无创检测(运动前和运动后检测--包括核灌注扫描)和有创检测(量化冠状动脉病变前后和血管内超声)进一步监测患者的状况。这些后一种检查对于解决特定的目标2和3尤为关键。我们预计，这项研究的结果应该确定安全性--并可能提供关于疗效的见解--这将有助于指导关于在第二阶段试验中进一步测试这一拟议治疗策略的价值的决定。

This Proposal has been designed to investigate arterial gene transfer of naked DNA encoding for the 165-amino acid isoform of the VEGF-1 (VEGF A) gene as an adjunct to PTCA. The Proposal has the following three Specific Aims. Specific Aim #1: to determine the safety of coronary gene transfer of phVEGF165 to accelerate re-endothelialization (rET) following percutaneous transluminal coronary angioplasty (PTCA) in patients (pts) with stenotic or occluded native coronary arteries. Specific Aim #2: to obtain preliminary data regarding bioactivity of coronary gene transfer of phVEGF165 for prevention of restonosis. Specific Aim #3: to determine the impact of phVEGF165 coronary gene transfer on the progression of atherosclerosis involving coronary arterial sites other than PTCA target sites. A variety of assessments will be performed among the patients enrolled in this study following gene transfer. Serial clinical examinations- including standard history and physical examinations-along with standard laboratory tests will be performed to document the safety of phVEGF165 coronary gene transfer. The patients' status will be further monitored by both non-invasive tests (pre- and post-exercise testing-including nuclear perfusion scans) and invasive testing )pre- and post-quantitative coronary angiopathy and intravascular ultrasound). These latter examinations will be particularly critical for addressing Specific Aims 2 and 3. It is our anticipation that the findings of this study should establish the safety- and potentially provide insights regarding efficacy- that would help to guide decisions regarding the value of testing this proposed therapeutic strategy further in Phase II trials.